Mechanisms of continence and surgical cure in female and male SUI: Surgical research initiatives

Aims To report the conclusions of the Think Tank on mechanisms of incontinence and surgical cure in female and male SUI: surgical research initiatives during the ICI‐RS meeting in 2010. Methods The sub‐group considered five areas for future research in stress urinary incontinence (SUI); (i) epidemiology and public health efforts in SUI, (ii) the basic sciences examining the physiology and pathophysiology of the continence mechanism, (iii) diagnostic techniques and clinical assessment of SUI, (iv) the future of treatment and surgical cure, and (v) the separate issue of male SUI. Results Roadblocks to progress were identified for each of the five directions. Conclusions Future research directions are suggested for each of these areas. Neurourol. Urodynam. 30:704–707, 2011. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87181/1/21139_ftp.pd

Efficacy and Safety of Once-Daily Vibegron for Treatment of Overactive Bladder in Patients Aged ≥65 and ≥75 Years: Subpopulation Analysis from the EMPOWUR Randomized, International, Phase III Study

Background Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years. Methods In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) episodes; a key secondary efficacy endpoint was change from baseline at week 12 in average daily number of urgency episodes. Safety was assessed through adverse events (AEs). Efficacy analyses compared vibegron with placebo; no efficacy comparisons were made between vibegron and tolterodine. Results Of the 1463 patients with evaluable efficacy data, 628 patients were aged ≥ 65 years, and 179 were aged ≥ 75 years. After 12 weeks, patients treated with once-daily vibegron 75 mg in both age subgroups showed significant improvements from baseline versus placebo in all three symptoms of OAB: daily micturitions (≥ 65 years, P \u3c 0.0001; ≥75 years, P \u3c 0.05), UUI episodes (≥ 65 years, P \u3c 0.001; ≥ 75 years, P \u3c 0.0001), and urgency episodes (≥ 65 years, P \u3c 0.01; ≥ 75 years, P \u3c 0.01). Significant reductions from baseline versus placebo in daily micturitions, UUI episodes, and urgency episodes were observed beginning at week 2 for patients aged ≥ 65 years treated with vibegron. In patients aged ≥ 65 years, 50.0% of those receiving vibegron versus 29.8% receiving placebo experienced a ≥ 75% reduction in UUI episodes at week 12 (P\u3c 0.0001). Rates of cardiovascular-associated AEs were low for patients receiving vibegron ( Conclusions In this subpopulation analysis of patients with OAB aged ≥ 65 and ≥ 75 years from the EMPOWUR study, once-daily vibegron 75 mg showed rapid onset and robust efficacy versus placebo and was generally safe and well tolerated, consistent with results from the overall population

EFFICACY, SAFETY, AND TOLERABILITY OF MIRABEGRON IN PATIENTS AGED ≥65 YR WITH OVERACTIVE BLADDER WET: A PHASE IV, DOUBLE-BLIND, RANDOMISED, PLACEBOCONTROLLED STUDY (PILLAR)

Pozadina: Većina bolesnika s prekomjerno aktivnim mokraćnim mjehurom (PAMM) starija je od 65 godina. Dosad nije bilo prospektivnih ispitivanja kojima bi se ocijenila djelotvornost liječenja agonistom β3-adrenoreceptora mirabegronom u ovoj specifi čnoj dobnoj skupini. Cilj: Ispitivanje faze IV u kojem se uspoređuju mirabegron u fl eksibilnoj dozi i placebo u starijih bolesnika s PAMM om i urgentnom inkontinencijom. Dizajn, uvjeti i sudionici: Bolesnici iz lokalne zajednice koji imaju ≥ 65 godina i PAMM u trajanju od ≥ 3 mjeseca. Intervencija: Nakon 2 tjednog uvodnog razdoblja tijekom kojeg se primjenjivao placebo bolesnici s jednom ili više epizoda inkontinencije, tri ili više epizoda urgencije i prosječno osam ili više mokrenja tijekom 24 h bili su randomizirani u omjeru 1:1 za dvostruko zaslijepljenu primjenu 25 mg mirabegrona ili odgovarajuće formulacije placeba na dan tijekom 12 tjedana. Nakon 4. ili 8. tjedna doza se prema odluci bolesnika i ispitivača mogla povećati na 50 mg mirabegrona/odgovarajuće formulacije placeba na dan. Mjere ishoda i statistička analiza: Primarne mjere ishoda: promjena srednjeg broja mokrenja tijekom 24 h i srednjeg broja epizoda inkontinencije tijekom 24 h od početka ispitivanja do završetka liječenja. Sekundarne mjere ishoda: promjena srednjeg izmokrenog volumena nakon mokrenja, srednjeg broja epizoda urgencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h od početka ispitivanja do završetka liječenja. Za ocjenu srednjeg broja mokrenja tijekom 24 h, srednjeg izmokrenog volumena nakon mokrenju i srednjeg broja epizoda urgencije tijekom 24 h koristila se analiza kovarijance (ANCOVA). Za ocjenu srednjeg broja epizoda inkontinencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h koristila se stratifi cirana rang ANCOVA. Rezultati i ograničenja: Uz mirabegron su opažena statistički značajna poboljšanja u odnosu na placebo s obzirom na promjenu srednjeg broja mokrenja tijekom 24 h, srednjeg broja epizoda inkontinencije tijekom 24 h, srednjeg izmokrenog volumena nakon mokrenja, srednjeg broja epizoda urgencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h od početka ispitivanja do završetka liječenja. Sigurnost i podnošljivost odgovarale su poznatom sigurnosnom profi lu mirabegrona. Zaključci: Potvrđene su djelotvornost, sigurnost i podnošljivost mirabegrona tijekom 12 tjedana u bolesnika s PAMM om i inkontinencijom u dobi od ≥ 65 godina. Sažetak za bolesnike: Ispitivali smo učinak mirabegrona u usporedbi s placebom u osoba u dobi od 65 ili više godina s prekomjerno aktivnim mokraćnim mjehurom i inkontinencijom. Mirabegron je ublažio simptome prekomjerno aktivnog mokraćnog mjehura u usporedbi s placebom. Opažene nuspojave bile su slične poznatim nuspojavama mirabegrona.Background: The majority of patients with overactive bladder (OAB) are aged >65 yr. There has been no prospectively designed study assessing treatment effi cacy with the b3-adrenoreceptor agonist, mirabegron, specifi cally in this age group. Objective: A phase IV study comparing fl exibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence. Design, setting, and participants: Community-dwelling patients aged ≥65 yr with OAB for ≥3 mo. Intervention: Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/ 24 h were randomised 1:1 to double-blind 25 mg/d mirabegron or matched placebo, for 12 wk. After week 4 or 8, the dose could be increased to 50 mg/d mirabegron/matched placebo based on patient and investigator discretion. Outcome measurements and statistical analysis: Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24 h and incontinence episodes/24 h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24 h, mean volume voided/micturition, and mean number of urgency episodes/24 h. Stratifi ed rank ANCOVA was used for the mean numbers of incontinence episodes/24 h and urgency incontinence episodes/24 h. Results and limitations: Statistically signifi cant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Safety and tolerability were consistent with the known mirabegron safety profi le. Conclusions: Mirabegron effi cacy, safety, and tolerability over 12 wk were confi rmed in patients aged ≥65 yr with OAB and incontinence

Validation of a bladder symptom screening tool in women with incontinence due to overactive bladder

Abstract Introduction and hypothesis The Actionable Bladder Symptom Screening Tool (ABSST) was initially developed to identify patients with multiple sclerosis (MS) who could benefit from lower urinary tract assessment and treatment. Assessment of the measurement properties of the ABSST, including its ability to identify patients experiencing bladder symptoms related to overactive bladder (OAB), was undertaken in a general female population. Methods One hundred women completed the ABSST, OAB Questionnaire Short Form (OAB-q SF), and a patient global impression of severity (PGI-S) scale. Half of the sample had urgency urinary incontinence (UUI), while the other half did not. Descriptive statistics, reliability, and validity were examined, as was sensitivity and specificity of the previous cut-off score established in MS. Results Fifty-three women with UUI/OAB and 47 controls took part (71.0 % Caucasian). Patients with UUI/OAB were older (54.6 vs 40.4 years), had a higher body mass index (31.1 vs 26.4 kg/m 2 ), and more comorbid conditions. The Cronbach's alpha reliability of ABSST was 0.90. High correlations with OAB-q SF Symptom Bother and Health Related Quality of Life (r=0.83 and −0.81 respectively) supported concurrent validity. Using the PGI-S severity scores as a reference, the ABSST was able to distinguish patients with differing severity levels (known-group validity). Physician assessment of the need for further evaluation/treatment showed sensitivity (79 %) and specificity (98 %), supporting a cut-off score of ≥3. Conclusions The previous MS ABSST scoring algorithm was validated in a non-neurogenic female population. ABSST is a reliable, valid, and sensitive tool for screening women with UUI/OAB

Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder

<p>Abstract</p> <p>Background</p> <p>Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine.</p> <p>Methods</p> <p>Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.</p> <p>Results</p> <p>The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively.</p> <p>Conclusions</p> <p>A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials.</p> <p>Trial Registration</p> <p>The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).</p